Department of Neurology, Institute of Neurology and the Collaborative Innovation Center for Brain Science, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Department of Neurology, Institute of Neurology and the Collaborative Innovation Center for Brain Science, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Laboratory of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Science & Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Prog Neurobiol. 2016 Dec;147:1-19. doi: 10.1016/j.pneurobio.2016.07.005. Epub 2016 Oct 18.
Oxidative stress reflects an imbalance between the overproduction and incorporation of free radicals and the dynamic ability of a biosystem to detoxify reactive intermediates. Free radicals produced by oxidative stress are one of the common features in several experimental models of diseases. Free radicals affect both the structure and function of neural cells, and contribute to a wide range of neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Although the precise mechanisms that result in the degeneration of neurons and the relevant pathological changes remain unclear, the crucial role of oxidative stress in the pathogenesis of neurodegenerative diseases is associated with several proteins (such as α-synuclein, DJ-1, Amyloid β and tau protein) and some signaling pathways (such as extracellular regulated protein kinases, phosphoinositide 3-kinase/Protein Kinase B pathway and extracellular signal-regulated kinases 1/2) that are tightly associated with the neural damage. In this review, we present evidence, gathered over the last decade, concerning a variety of pathogenic proteins, their important signaling pathways and pathogenic mechanisms associated with oxidative stress in Parkinson's disease and Alzheimer's disease. Proper control and regulation of these proteins' functions and the related signaling pathways may be a promising therapeutic approach to the patients. We also emphasizes antioxidative options, including some new neuroprotective agents that eliminate excess reactive oxygen species efficiently and have a certain therapeutic effect; however, controversy surrounds some of them in terms of the dose and length of therapy. These agents require further investigation by clinical application in patients suffering Parkinson's disease and Alzheimer's disease.
氧化应激反映了自由基的过度产生和积累与生物系统解毒反应中间体的动态能力之间的失衡。氧化应激产生的自由基是几种疾病实验模型的共同特征之一。自由基影响神经细胞的结构和功能，并导致广泛的神经退行性疾病，包括帕金森病和阿尔茨海默病。尽管导致神经元退化和相关病理变化的确切机制尚不清楚，但氧化应激在神经退行性疾病发病机制中的关键作用与几种蛋白质（如α-突触核蛋白、DJ-1、淀粉样β和tau 蛋白）和一些信号通路（如细胞外调节蛋白激酶、磷酸肌醇 3-激酶/蛋白激酶 B 通路和细胞外信号调节激酶 1/2）密切相关，这些信号通路与神经损伤有关。在这篇综述中，我们展示了过去十年中积累的证据，涉及各种致病蛋白、它们与帕金森病和阿尔茨海默病中氧化应激相关的重要信号通路及其发病机制。适当控制和调节这些蛋白质的功能和相关信号通路可能是治疗这些患者的一种有前途的方法。我们还强调了抗氧化选择，包括一些新的神经保护剂，它们可以有效地清除过多的活性氧，并具有一定的治疗效果；然而，其中一些在剂量和治疗时间方面存在争议。这些药物需要通过对帕金森病和阿尔茨海默病患者的临床应用进一步研究。
